This project focuses on developing a better understanding of the mechanisms involved in virus-induced leukemogenesis. Specifically this project deals with host-controlled susceptibility to a murine erythroleukemia virus. Fv-2 is a gene in the mouse that modifies susceptibility to a single oncogenic virus, the Spleen Focus-Forming Virus (SFFV). Mice homozygous for the Fv-2r allele (e.g., C57BL/6) are completely resistant to transformation by the spleen focus-forming virus (1). The experiments in this project are devised to characterize the Friend virus-like disease that develops in resistant mice infected with Fv-2rr-adapted strains of Friend Virus. Experiments are proposed that will examine several alternate theories on how the variants acquired the new host range. The studies will examine the possibility that the variants infect progenitor cells at a different stage of differentiation than that infected by the wild-type virus. In addition, the project proposes to clone the Fv-2rr-adapted viruses. The cloned variants will then be analyzed by generating recombinant with wild-type virus and by sequencing the env gene of the variants. The results from this project will enhance our understanding of viral-host interactions, virus-induced transformation, and genetic control of erythroid differentiation.